A Quantitative Approach for Detecting Anxiolytic Drug Effects in the Mouse

检测小鼠抗焦虑药物作用的定量方法

• 批准号: 7305447
• 负责人: Laurence H. Tecott
• 金额: $ 20.8万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-17 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7305447
• 关键词: Acute; Anti-Anxiety Agents; Antidepressive Agents; Anxiety; Anxiety Disorders; BALB/cJ Mouse; Behavior; Behavior assessment; Behavioral; Behavioral Assay; Biological Assay; Buspirone; Characteristics; Chlordiazepoxide; Chronic; Complex; Data; Data Set; Desipramine; Detection; Development; Diazepam; Exhibits; Exploratory Behavior; Fluoxetine; Genes; Genetic; Goals; Home environment; Inbred Strains Mice; Light; Measures; Methods; Monitor; Motor Activity; Mouse Strains; Mus; Mutation; Neurons; Pattern; Pentylenetetrazole; Pharmaceutical Preparations; Piperazines; Procedures; Property; Purpose; Range; Regulation; Reproducibility; Resolution; Rest; Selective Serotonin Reuptake Inhibitor; Serotonin; Serotonin Receptor 5-HT2C; Spatial Distribution; Specificity; Standards of Weights and Measures; Stimulus; System; Testing; Therapeutic; Therapeutic Agents; Tricyclic Antidepressive Agents; Validation; base; behavior measurement; environmental stressor; feeding; genetic resource; neuromechanism; novel; novel strategies; novel therapeutics; piperazine; relating to nervous system; response; restraint stress; reuptake; stressor; tool

DESCRIPTION (provided by applicant): The proliferation of mouse lines bearing mutations of neural genes presents new opportunities for inroads into the neural bases of complex behaviors, such as the regulation of anxiety. Our ability to optimally utilize mouse genetic resources for this purpose is critically dependent on the reliability and sensitivity of behavioral assays. Although standard approaches for assessing anxiety-related behavior in mice have been of substantial benefit, widely recognized limitations in the accuracy, sensitivity and reproducibility of such assays warrant initiatives for the development of novel complementary approaches. We propose to adapt a unique quantitative approach to the analysis of mouse home cage behavior to this problem. We will test the hypothesis that environmental and pharmacological manipulations that modulate anxiety will impact the coordinated expression of spontaneous behaviors exhibited by mice in their home cages. We propose that quantitative analysis of high-resolution home cage behavioral datasets can be adapted to provide a highly sensitive assessment of novel anxiety- related behavioral measures. The proposal consists of 3 Aims. In Aim 1 we will examine the sensitivity of home cage behavioral patterns to stressors, with the goal of identifying potential candidate anxiety measures. Two inbred mouse strains believed to differ in their expression of anxiety-related behaviors will be used. In Aim 2, a pharmacological validation approach will be taken to assess the extent to which these measures are appropriately modified by known anxiolytic and anxiogenic drugs. The specificity of these measures will be explored by examining their sensitivity to behaviorally active drugs not known to modulate anxiety. In Aim 3, we will determine the extent to which quantitative home cage behavioral monitoring approaches may be used to detect slow-onset anxiolytic effects produced by chronic treatment with the serotonin reuptake blocker fluoxetine and the tricyclic antidepressant desipramine. Strains of mice known to respond differently to chronic fluoxetine treatment, C57BL/6J and BALB/cJ, will be used for these studies. Limitations in behavioral assessment methods for determining anxiety levels in the mouse are hindering the development of novel therapeutic agents for anxiety disorders. Here we propose to adapt a novel quantitative behavioral monitoring method we have developed to derive and validate new markers of anxiety state.

描述（由申请人提供）：携带神经基因突变的小鼠品系的增殖为侵入复杂行为的神经基础提供了新的机会，例如焦虑的调节。我们的能力，以最佳方式利用小鼠遗传资源，用于这一目的是严重依赖于行为测定的可靠性和灵敏度。尽管用于评估小鼠中焦虑相关行为的标准方法已经具有实质性益处，但广泛公认的此类测定的准确性、灵敏度和再现性的局限性保证了开发新的补充方法的倡议。我们建议采用一种独特的定量方法来分析这个问题的小鼠的家笼行为。我们将检验调节焦虑的环境和药理学操作将影响小鼠在其家庭笼中表现出的自发行为的协调表达的假设。我们建议，高分辨率的家庭笼行为数据集的定量分析，可以适应提供一个高度敏感的评估新的焦虑相关的行为措施。该提案包括三个目标。在目标1中，我们将研究笼舍行为模式对压力源的敏感性，目的是确定潜在的候选焦虑措施。将使用两种被认为在焦虑相关行为的表达方面不同的近交系小鼠品系。在目标2中，将采用药理学验证方法来评估已知抗焦虑和致焦虑药物对这些措施进行适当修改的程度。这些措施的特异性将通过检查其敏感性行为活性药物不知道调节焦虑。在目标3中，我们将确定定量笼行为监测方法可用于检测5-羟色胺再摄取阻滞剂氟西汀和三环类抗抑郁药地昔帕明长期治疗产生的缓慢起效的抗焦虑作用的程度。这些研究将使用已知对长期氟西汀治疗反应不同的小鼠品系C57 BL/6 J和BALB/cJ。用于确定小鼠中焦虑水平的行为评估方法的局限性阻碍了焦虑障碍的新型治疗剂的开发。在这里，我们建议采用一种新的定量行为监测方法，我们已经开发出衍生和验证焦虑状态的新标志物。